Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor

• Verfasst von: Yousefi, Omid Sascha [VerfasserIn]
• Verfasst von: Günther, Matthias [VerfasserIn]
• Verfasst von: Höfer, Thomas [VerfasserIn]
• Titel: Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor
• Verf.angabe: O Sascha Yousefi, Matthias Günther, Maximilian Hörner, Julia Chalupsky, Maximilian Wess, Simon M Brandl, Robert W Smith, Christian Fleck, Tim Kunkel, Matias D Zurbriggen, Thomas Höfer, Wilfried Weber, Wolfgang WA Schamel
• E-Jahr: 2019
• Jahr: 05 April 2019
• Umfang: 33 S.
• Fussnoten: Gesehen am 23.07.2019
• Titel Quelle: Enthalten in: eLife
• Ort Quelle: Cambridge : eLife Sciences Publications, 2012
• Jahr Quelle: 2019
• Band/Heft Quelle: 8(2019) Artikel-Nummer e42475, 33 Seiten
• ISSN Quelle: 2050-084X
• DOI: doi:10.7554/eLife.42475
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: dynamics
• Sach-SW: ligand-receptor
• Sach-SW: optogenetics
• Sach-SW: signaling
• Sach-SW: T cells
• K10plus-PPN: 1669599507

Abstract

The immune system distinguishes between self and foreign antigens. The kinetic proofreading (KPR) model proposes that T cells discriminate self from foreign ligands by the different ligand binding half-lives to the T cell receptor (TCR). It is challenging to test KPR as the available experimental systems fall short of only altering the binding half-lives and keeping other parameters of the interaction unchanged. We engineered an optogenetic system using the plant photoreceptor phytochrome B (PhyB) as a ligand to selectively control the dynamics of ligand binding to the TCR by light. This opto-ligand-TCR system was combined with the unique property of PhyB to continuously cycle between the binding and non-binding states under red light, with the light intensity determining the cycling rate and thus the binding duration. Mathematical modeling of our experimental datasets showed that indeed the ligand-TCR interaction half-life is the decisive factor for activating downstream TCR signaling, substantiating KPR.